No Access Submitted: 14 November 2019 Accepted: 18 February 2020 Published Online: 25 March 2020
Review of Scientific Instruments 91, 031301 (2020); https://doi.org/10.1063/1.5138210
more...View Affiliations
View Contributors
  • David J. Niedzwiecki
  • Yung-Chien Chou
  • Zehui Xia
  • Federico Thei
  • Marija Drndić
Nanopore sensing is a powerful tool for the detection of biomolecules. Solid-state nanopores act as single-molecule sensors that can function in harsh conditions. Their resilient nature makes them attractive candidates for taking this technology into the field to measure environmental samples for life detection in space and water quality monitoring. Here, we discuss the fabrication of silicon nitride pores from ∼1.6 to 20 nm in diameter in 20-nm-thick silicon nitride membranes suspended on glass chips and their performance. We detect pure laboratory samples containing a single analyte including DNA, BSA, microRNA, TAT, and poly-D-lys-hydrobromide. We also measured an environmental (mixed-analyte) sample, containing Antarctic dirt provided by NASA Ames. For DNA measurements, in addition to using KCl and NaCl solutions, we used the artificial (synthetic) seawater, which is a mixture of different salts mimicking the composition of natural seawater. These samples were spiked with double-stranded DNA (dsDNA) fragments at different concentrations to establish the limits of nanopore sensitivity in candidate environment conditions. Nanopore chips were cleaned and reused for successive measurements. A stand-alone, 1-MHz-bandwidth Chimera amplifier was used to determine the DNA concentration in artificial seawater that we can detect in a practical time scale of a few minutes. We also designed and developed a new compact nanopore reader, a portable read-out device with miniaturized fluidic cells, which can obtain translocation data at bandwidths up to 100 kHz. Using this new instrument, we record translocations of 400 bp, 1000 bp, and 15000 bp dsDNA fragments and show discrimination by analysis of current amplitude and event duration histograms.
The glass chips and nanopores were fabricated at the Pennovation Center and at the University of Pennsylvania’s Singh Center for Nanotechnology and at Rutgers University by Goeppert LLC. We thank Dr. Chris McKay from NASA Ames for providing samples of the Linnaeus Terrace dirt from Antarctic Dry Valleys. We also thank Jacob Swett at the University of Oxford for useful discussions and Michele Rossi, previously at Elements, SRL, for help with the portable nanopore reader. The nanopore reader and fluidic cell were developed here in collaboration with Elements, SRL, Italy. The work was supported by NASA SBIR Phase I No. S.11-3492 (2018-1) “Detecting life in ocean worlds with low-capacitance solid-state nanopores.” This work was carried out in part at the Singh Center for Nanotechnology, which is supported by the NSF National Nanotechnology Coordinated Infrastructure Program under Grant No. NNCI-1542153.
  1. 1. J. J. Kasianowicz, E. Brandin, D. Branton, and D. W. Deamer, Proc. Natl. Acad. Sci. U. S. A. 93, 13770 (1996). https://doi.org/10.1073/pnas.93.24.13770, Google ScholarCrossref, ISI
  2. 2. D. Branton, D. W. Deamer, A. Marziali, H. Bayley, S. A. Benner, T. Butler, M. Di Ventra, S. Garaj, A. Hibbs, X. Huang, S. B. Jovanovich, P. S. Krstic, S. Lindsay, X. S. Ling, C. H. Mastrangelo, A. Meller, J. S. Oliver, Y. V. Pershin, J. M. Ramsey, R. Riehn, G. V. Soni, V. Tabard-Cossa, M. Wanunu, M. Wiggin, and J. A. Schloss, Nat. Biotechnol. 26, 1146 (2008). https://doi.org/10.1038/nbt.1495, Google ScholarCrossref, ISI
  3. 3. M. Akeson, D. Branton, J. J. Kasianowicz, E. Brandin, and D. W. Deamer, Biophys. J. 77, 3227 (1999). https://doi.org/10.1016/s0006-3495(99)77153-5, Google ScholarCrossref
  4. 4. O. K. Dudko, J. Mathé, A. Szabo, A. Meller, and G. Hummer, Biophys. J. 92, 4188 (2007). https://doi.org/10.1529/biophysj.106.102855, Google ScholarCrossref
  5. 5. K. Healy, B. Schiedt, I. P. Morrison, and A. P. Morrison, Nanomedicine 2, 875 (2007). https://doi.org/10.2217/17435889.2.6.875, Google ScholarCrossref
  6. 6. T. Z. Butler, M. Pavlenok, I. M. Derrington, M. Niederweis, and J. H. Gundlach, Proc. Natl. Acad. Sci. U. S. A. 105, 20647 (2008). https://doi.org/10.1073/pnas.0807514106, Google ScholarCrossref
  7. 7. M. Wanunu, W. Morrison, Y. Rabin, A. Y. Grosberg, and A. Meller, Nat. Nanotechnol. 5, 160 (2010). https://doi.org/10.1038/nnano.2009.379, Google ScholarCrossref
  8. 8. R. Kawano, A. E. P. P. Schibel, C. Cauley, and H. S. White, Langmuir 25, 1233 (2009). https://doi.org/10.1021/la803556p, Google ScholarCrossref
  9. 9. L.-Q. Gu and J. W. Shim, Analyst 135, 441 (2010). https://doi.org/10.1039/b907735a, Google ScholarCrossref
  10. 10. Z. S. Siwy and S. Howorka, Chem. Soc. Rev. 39, 1115 (2010). https://doi.org/10.1039/b909105j, Google ScholarCrossref, ISI
  11. 11. S. W. Kowalczyk, A. R. Hall, and C. Dekker, Nano Lett. 10, 324 (2010). https://doi.org/10.1021/nl903631m, Google ScholarCrossref
  12. 12. K. R. Lieberman, G. M. Cherf, M. J. Doody, F. Olasagasti, Y. Kolodji, and M. Akeson, J. Am. Chem. Soc. 132, 17961 (2010). https://doi.org/10.1021/ja1087612, Google ScholarCrossref
  13. 13. C. A. Merchant, K. Healy, M. Wanunu, V. Ray, N. Peterman, J. Bartel, M. D. Fischbein, K. Venta, Z. Luo, A. T. C. C. Johnson, and M. Drndić, Nano Lett. 10, 2915 (2010). https://doi.org/10.1021/nl101046t, Google ScholarCrossref, ISI
  14. 14. D. W. Deamer and M. Akeson, Trends Biotechnol. 18, 147 (2000). https://doi.org/10.1016/s0167-7799(00)01426-8, Google ScholarCrossref
  15. 15. S. Garaj, W. Hubbard, A. Reina, J. Kong, D. Branton, and J. A. Golovchenko, Nature 467, 190 (2010). https://doi.org/10.1038/nature09379, Google ScholarCrossref, ISI
  16. 16. U. Mirsaidov, J. Comer, V. Dimitrov, A. Aksimentiev, and G. Timp, Nanotechnology 21, 395501 (2010). https://doi.org/10.1088/0957-4484/21/39/395501, Google ScholarCrossref
  17. 17. J. E. Reiner, J. J. Kasianowicz, B. J. Nablo, and J. W. F. F. Robertson, Proc. Natl. Acad. Sci. U. S. A. 107, 12080 (2010). https://doi.org/10.1073/pnas.1002194107, Google ScholarCrossref
  18. 18. M. Wanunu, Phys. Life Rev. 9, 125 (2012). https://doi.org/10.1016/j.plrev.2012.05.010, Google ScholarCrossref
  19. 19. W. Timp, J. Comer, and A. Aksimentiev, Biophys. J. 102, L37 (2012). https://doi.org/10.1016/j.bpj.2012.04.009, Google ScholarCrossref
  20. 20. E. A. Manrao, I. M. Derrington, A. H. Laszlo, K. W. Langford, M. K. Hopper, N. Gillgren, M. Pavlenok, M. Niederweis, and J. H. Gundlach, Nat. Biotechnol. 30, 349 (2012). https://doi.org/10.1038/nbt.2171, Google ScholarCrossref
  21. 21. S. W. Kowalczyk, D. B. Wells, A. Aksimentiev, C. Dekker, P. Susan, S. W. Kowalczyk, D. B. Wells, A. Aksimentiev, and C. Dekker, Nano Lett. 12, 1038 (2012). https://doi.org/10.1021/nl204273h, Google ScholarCrossref
  22. 22. R. Wei, T. G. Martin, U. Rant, and H. Dietz, Angew. Chem., Int. Ed. 51, 4864 (2012). https://doi.org/10.1002/anie.201200688, Google ScholarCrossref
  23. 23. M. Langecker, V. Arnaut, T. G. Martin, J. List, S. Renner, M. Mayer, H. Dietz, and F. C. Simmel, Science 338, 932 (2012). https://doi.org/10.1126/science.1225624, Google ScholarCrossref
  24. 24. B. Luan, D. Wang, R. Zhou, S. Harrer, H. Peng, and G. Stolovitzky, Nanotechnology 23, 455102 (2012). https://doi.org/10.1088/0957-4484/23/45/455102, Google ScholarCrossref
  25. 25. A. Meller and D. Branton, Electrophoresis 23, 2583 (2002). https://doi.org/10.1002/1522-2683(200208)23:16<2583::aid-elps2583>3.0.co;2-h, Google ScholarCrossref
  26. 26. J. K. Rosenstein, M. Wanunu, C. A. Merchant, M. Drndic, and K. L. Shepard, Nat. Methods 9, 487 (2012). https://doi.org/10.1038/nmeth.1932, Google ScholarCrossref
  27. 27. G. M. Cherf, K. R. Lieberman, H. Rashid, C. E. Lam, K. Karplus, and M. Akeson, Nat. Biotechnol. 30, 344 (2012). https://doi.org/10.1038/nbt.2147, Google ScholarCrossref
  28. 28. K. Venta, G. Shemer, M. Puster, J. A. Rodríguez-Manzo, A. Balan, J. K. Rosenstein, K. Shepard, and M. Drndić, ACS Nano 7, 4629 (2013). https://doi.org/10.1021/nn4014388, Google ScholarCrossref
  29. 29. Y. He, M. Tsutsui, R. H. Scheicher, F. Bai, M. Taniguchi, and T. Kawai, ACS Nano 7, 538 (2013). https://doi.org/10.1021/nn304914j, Google ScholarCrossref
  30. 30. A. Balan, B. Machielse, D. Niedzwiecki, J. Lin, P. Ong, R. Engelke, K. L. Shepard, and M. Drndić, Nano Lett. 14, 7215 (2014). https://doi.org/10.1021/nl504345y, Google ScholarCrossref
  31. 31. A. Balan, C.-C. Chien, R. Engelke, and M. Drndić, Sci. Rep. 5, 17775 (2015). https://doi.org/10.1038/srep17775, Google ScholarCrossref
  32. 32. S. Shekar, D. J. Niedzwiecki, C.-C. Chien, P. Ong, D. A. Fleischer, J. Lin, J. K. Rosenstein, M. Drndić, and K. L. Shepard, Nano Lett. 16, 4483 (2016). https://doi.org/10.1021/acs.nanolett.6b01661, Google ScholarCrossref
  33. 33. M. Jain, S. Koren, K. H. Miga, J. Quick, A. C. Rand, T. A. Sasani, J. R. Tyson, A. D. Beggs, A. T. Dilthey, I. T. Fiddes, S. Malla, H. Marriott, T. Nieto, J. O’Grady, H. E. Olsen, B. S. Pedersen, A. Rhie, H. Richardson, A. R. Quinlan, T. P. Snutch, L. Tee, B. Paten, A. M. Phillippy, J. T. Simpson, N. J. Loman, and M. Loose, Nat. Biotechnol. 36, 338 (2018). https://doi.org/10.1038/nbt.4060, Google ScholarCrossref
  34. 34. G. Danda and M. Drndić, Curr. Opin. Biotechnol. 55, 124 (2019). https://doi.org/10.1016/j.copbio.2018.09.002, Google ScholarCrossref
  35. 35. A. J. Storm, J. H. Chen, X. S. Ling, H. W. Zandbergen, and C. Dekker, Nat. Mater. 2, 537 (2003). https://doi.org/10.1038/nmat941, Google ScholarCrossref, ISI
  36. 36. D. Fologea, M. Gershow, B. Ledden, D. S. McNabb, J. A. Golovchenko, and J. Li, Nano Lett. 5, 1905 (2005). https://doi.org/10.1021/nl051199m, Google ScholarCrossref, ISI
  37. 37. U. F. Keyser, B. N. Koeleman, S. Van Dorp, D. Krapf, R. M. M. M. Smeets, S. G. Lemay, N. H. Dekker, and C. Dekker, Nat. Phys. 2, 473 (2006). https://doi.org/10.1038/nphys344, Google ScholarCrossref, ISI
  38. 38. M. Rhee and M. A. Burns, Trends Biotechnol. 24, 580 (2006). https://doi.org/10.1016/j.tibtech.2006.10.005, Google ScholarCrossref
  39. 39. J. W. F. Robertson, C. G. Rodrigues, V. M. Stanford, K. A. Rubinson, O. V. Krasilnikov, and J. J. Kasianowicz, Proc. Natl. Acad. Sci. U. S. A. 104, 8207 (2007). https://doi.org/10.1073/pnas.0611085104, Google ScholarCrossref
  40. 40. R. M. M. Smeets, U. F. Keyser, N. H. Dekker, and C. Dekker, Proc. Natl. Acad. Sci. U. S. A. 105, 417 (2008). https://doi.org/10.1073/pnas.0705349105, Google ScholarCrossref
  41. 41. K. M. Halverson, R. G. Panchal, T. L. Nguyen, R. Gussio, S. F. Little, M. Misakian, S. Bavari, and J. J. Kasianowicz, J. Biol. Chem. 280, 34056 (2005). https://doi.org/10.1074/jbc.m507928200, Google ScholarCrossref
  42. 42. M. Wanunu, T. Dadosh, V. Ray, J. Jin, L. McReynolds, and M. Drndić, Nat. Nanotechnol. 5, 807 (2010). https://doi.org/10.1038/nnano.2010.202, Google ScholarCrossref
  43. 43. K. E. Venta, M. B. Zanjani, X. Ye, G. Danda, C. B. Murray, J. R. Lukes, and M. Drndić, Nano Lett. 14, 5358 (2014). https://doi.org/10.1021/nl502448s, Google ScholarCrossref
  44. 44. W. H. Coulter, U.S. patent 2656508 (October 20, 1953). Google Scholar
  45. 45. S. A. Benner, Astrobiology 17, 840 (2017). https://doi.org/10.1089/ast.2016.1611, Google ScholarCrossref
  46. 46. A. F. Davila and C. P. McKay, Astrobiology 14, 534 (2014). https://doi.org/10.1089/ast.2014.1150, Google ScholarCrossref
  47. 47. F. Rezzonico, Astrobiology 14, 344 (2014). https://doi.org/10.1089/ast.2013.1120, Google ScholarCrossref
  48. 48. K. F. Bywaters, C. P. McKay, A. F. Davila, and R. C. Quinn, in Proceedings of Conference on Biosignature Preservation and Detection in Mars Analog Environments, Lake Tahoe, NV, 16–18 May 2016, paper 2014. Google Scholar
  49. 49. S. S. Johnson, E. Zaikova, D. S. Goerlitz, Y. Bai, and S. W. Tighe, J. Biomol. Tech. 28, 2 (2017). https://doi.org/10.7171/jbt.17-2801-009, Google ScholarCrossref
  50. 50. A. Mojarro, J. Hachey, R. Bailey, M. Brown, R. Doebler, G. Ruvkun, M. T. Zuber, and C. E. Carr, Astrobiology 19, 1139 (2019). https://doi.org/10.1089/ast.2018.1929, Google ScholarCrossref
  51. 51. S. L. Castro-Wallace, C. Y. Chiu, K. K. John, S. E. Stahl, K. H. Rubins, A. B. R. McIntyre, J. P. Dworkin, M. L. Lupisella, D. J. Smith, D. J. Botkin, T. A. Stephenson, S. Juul, D. J. Turner, F. Izquierdo, S. Federman, D. Stryke, S. Somasekar, N. Alexander, G. Yu, C. E. Mason, and A. S. Burton, Sci. Rep. 7, 18022 (2017). https://doi.org/10.1038/s41598-017-18364-0, Google ScholarCrossref
  52. 52. K. B. Bywaters, H. J. Schmidt, W. Vercoutere, D. Deamer, A. R. Hawkins, R. C. Quinn, A. S. Burton, and C. P. McKay, ECS Meet. Abstr. MA2019-02, 2467 (2019). https://doi.org/10.1149/MA2019-02/57/2476, Google ScholarCrossref
  53. 53. W. D. Williams, Mar. Freshwater Res. 37, 177 (1986). https://doi.org/10.1071/mf9860177, Google ScholarCrossref
  54. 54. D. R. Kester, I. W. Duedall, D. N. Connors, and R. M. Pytkowicz, Limnol. Oceanogr. 12, 176 (1967). https://doi.org/10.4319/lo.1967.12.1.0176, Google ScholarCrossref
  55. 55. W.-H. Chuang, T. Luger, R. K. Fettig, and R. Ghodssi, J. Microelectromech. Syst. 13, 870 (2004). https://doi.org/10.1109/jmems.2004.836815, Google ScholarCrossref
  56. 56. I. Chakraborty, W. C. Tang, D. P. Bame, and T. K. Tang, Sens. Actuators, A 83, 188 (2000). https://doi.org/10.1016/s0924-4247(99)00382-9, Google ScholarCrossref
  57. 57. J. J. Bock, J. Glenn, S. M. Grannan, K. D. Irwin, A. E. Lange, H. G. LeDuc, and A. D. Turner, Proc. SPIE 3357, 297–304 (1998). https://doi.org/10.1117/12.317365, Google ScholarCrossref
  58. 58. L. C. Martin, J. D. Wrbanek, and G. C. Fralick, in ICIASF 2001 Record of 19th International Congress Instrumentation in Aerospace Simulation Facilities (Cat. No.01CH37215) (University of Michigan, 2001), pp. 196–203. Google Scholar
  59. 59. J. A. Rodríguez-Manzo, M. Puster, A. Nicolaï, V. Meunier, and M. Drndić, ACS Nano 9, 6555 (2015). https://doi.org/10.1021/acsnano.5b02531, Google ScholarCrossref
  60. 60. M. D. Fischbein and M. Drndić, Nano Lett. 7, 1329 (2007). https://doi.org/10.1021/nl0703626, Google ScholarCrossref, ISI
  61. 61. C.-C. C. Chien, S. Shekar, D. J. Niedzwiecki, K. L. Shepard, and M. Drndić, ACS Nano 13, 010545 (2019). https://doi.org/10.1021/acsnano.9b04626, Google ScholarCrossref
  62. 62. M. Waugh, K. Briggs, D. Gunn, M. Gibeault, S. King, Q. Ingram, A. M. Jimenez, S. Berryman, D. Lomovtsev, L. Andrzejewski, and V. Tabard-Cossa, Nat. Protoc. 15, 122 (2020). https://doi.org/10.1038/s41596-019-0255-2, Google ScholarCrossref
  63. 63. G. Danda, P. Masih Das, Y.-C. Chou, J. T. Mlack, W. M. Parkin, C. H. Naylor, K. Fujisawa, T. Zhang, L. B. Fulton, M. Terrones, A. T. C. Johnson, and M. Drndić, ACS Nano 11, 1937 (2017). https://doi.org/10.1021/acsnano.6b08028, Google ScholarCrossref
  64. 64. G. Danda, P. Masih Das, and M. Drndić, 2D Mater. 5, 035011 (2018). https://doi.org/10.1088/2053-1583/aabb73, Google ScholarCrossref
  65. 65. T. Gilboa, E. Zvuloni, A. Zrehen, A. H. Squires, and A. Meller, Adv. Funct. Mater. (published online). https://doi.org/10.1002/adfm.201900642, Google ScholarCrossref
  66. 66. H. Yamazaki, R. Hu, Q. Zhao, and M. Wanunu, ACS Nano 12, 012472 (2018). https://doi.org/10.1021/acsnano.8b06805, Google ScholarCrossref
  67. 67. C. L. C. Ip, M. Loose, J. R. Tyson, M. de Cesare, B. L. Brown, M. Jain, R. M. Leggett, D. A. Eccles, V. Zalunin, J. M. Urban, P. Piazza, R. J. Bowden, B. Paten, S. Mwaigwisya, E. M. Batty, J. T. Simpson, T. P. Snutch, E. Birney, D. Buck, S. Goodwin, H. J. Jansen, J. O’Grady, H. E. Olsen, and MinION Analysis and Reference Consortium, F1000Research 4, 1075 (2015). https://doi.org/10.12688/f1000research.7201.1, Google ScholarCrossref
  68. 68. A. K. Wright and M. R. Thompson, Biophys. J. 15, 137 (1975). https://doi.org/10.1016/s0006-3495(75)85797-3, Google ScholarCrossref
  1. © 2020 Author(s). Published under license by AIP Publishing.